Targeting the assembly of biomolecules: condensate-based drug discovery

Biomolecular condensates formed through liquid-liquid phase separation (LLPS) are widely regarded as a fundamental mode of cellular organization. Many intractable diseases, including cancer and neurodegenerative disorders, are increasingly linked to dysregulated biomolecular condensates. Aberrant condensates can serve as phenotypic markers for discovering drugs that target these challenging diseases. In this review, we discuss three main approaches for identifying hit compounds that modulate LLPS: condensate phenotype-based screening, compound repurposing, and rational design. We also highlight the importance of understanding LLPS mechanisms and their central role in guiding drug discovery and optimization. Despite the many remaining challenges, condensate-based drug discovery represents a highly compelling paradigm for next-generation therapeutics.